The proposed investigation will center on the synthesis and single crystal X-ray structural characterization of new cyclic phosphate compounds. Tetra- and pentacoordinated derivatives will be chosen which resemble active site substrates, intermediates, and transition states in enzymatic reactions. The studies will include oxy, thio, and amino ligands as hetero atoms in four-, five-, and six-membered rings. Solution and solid state studies by infrared and laser Raman and solution nmr studies will characterize conformational changes. The results will be used to parameterize a computer based model designed to simulate the active site structure of ribonuclease action. Structural perturbations caused by enzyme constraints, particularly hydrogen bonding, will be ascertained and used to refine the model. The dinucleotide UpA will serve as the initial model substrate. It is expected that alteration in the composition of the dinucleotide will result in conformationally minimized structures which reflect differences in substrate-transition state energies that correlate well with known enzyme rates.